Abstract
Hyperuricemia is defined as a disease with high uric acid (UA) levels in the blood and a strong risk factor for gout. Urolithin A (UroA) is a main microbial metabolite derived from ellagic acid (EA), which occurs in strawberries and pomegranates. In this study, we evaluated antihyperuricemic effect of UroA in both cultured hepatocytes and hyperuricemic model mice. In cultured hepatocytes, UroA significantly and dose-dependently reduced UA production. In model mice with purine bodies-induced hyperuricemia, oral administration of UroA significantly inhibited the increase in plasma UA levels and hepatic xanthine oxidase (XO) activity. In addition, DNA microarray results exhibited that UroA, as well as allopurinol, a strong XO inhibitor, induced downregulation of the expression of genes associated with hepatic purine metabolism. Thus, hypouricemic effect of UroA could be, at least partly, attributed to inhibition of purine metabolism and UA production by suppressing XO activity in the liver. These results indicate UroA possesses a potent antihyperuricemic effect and it could be a potential candidate for a molecule capable of preventing and improving hyperuricemia and gout.
Highlights
Hyperuricemia is the state characterized by abnormally high blood uric acid (UA) levels and caused by overproduction of UA mainly in the liver and/or reduced excretion from the kidney [1].Hyperuricemia is regarded as an important risk factor for gout and thought to increase the risk of other symptoms such as metabolic syndrome and renal disorders [2,3,4]
The effects of ellagic acid (EA), Urolithin A (UroA), and Urolithin B (UroB) on the cell viability of AML12 hepatocytes were first assessed using WST-8 assay in this study
(model control group) than 2C), that we of into mice into significantly increased the plasma UA level
Summary
Hyperuricemia is the state characterized by abnormally high blood uric acid (UA) levels and caused by overproduction of UA mainly in the liver and/or reduced excretion from the kidney [1]. Hyperuricemia is regarded as an important risk factor for gout and thought to increase the risk of other symptoms such as metabolic syndrome and renal disorders [2,3,4]. High levels of consumption of purine-rich foods such as meats, seafood, and purine-rich vegetables are associated with an increased risk of gout [5]. Xanthine oxidase (XO) in the liver is the key enzyme of UA production, and urate transporters including URAT1, GLUT9, and OAT1 in the kidney are the main transporters for the excretion of UA [1]. UA production-suppressive drugs (e.g., allopurinol and febuxostat, potent XO inhibitors) and Molecules 2020, 25, 5136; doi:10.3390/molecules25215136 www.mdpi.com/journal/molecules
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